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<p>Geniposidic acid (GPA) is a bioactive iridoid glycoside mainly found in many traditional medicinal plants, including <i>Eucommia ulmoides</i> and <i>Gardenia jasminoides</i>. These plants are also commonly used in traditional diets and herbal teas throughout East Asia, particularly in China and Japan, where they are used to maintain well-being and protect the respiratory, cardiovascular, and renal systems. Despite the growing number of individual studies that highlight GPA’s therapeutic potential, to date, there has been a lack of a systematic, critical synthesis of current knowledge. The aim of this review is to summarize the available information regarding the natural sources, methods of extraction, chemical structure, and biological and therapeutic actions of GPA. Data were obtained from PubMed, Scopus, and Web of Science, as well as reports published up to 2025. Evidence shows that GPA exerts manifold biological activities. The pharmacological actions in various disease models, including inflammatory, metabolic syndromes, neurodegenerative, cardiovascular, renal, and hepatic diseases and their mechanisms of action were discussed. The protective actions of GPA are associated with modulation of multiple cellular signaling pathways, including NF-<i>κ</i>B, NRF2/HO-1, PI3K/AKT, FXR, and TGF-<i>β</i> signaling, as well as inhibition of NLRP3 inflammasome activation. However, direct molecular target validation has only been demonstrated for selected pathways, particularly FXR and NLRP3, whereas most mechanistic evidence remains based on downstream signaling observations. Although preclinical studies in cells and animals demonstrate that GPA is effective, poor bioavailability remains one major limiting factor. Furthermore, comprehensive pharmacokinetic, toxicological, safety profiling, and well-designed clinical studies are required to support the clinical translation of GPA. This review identifies knowledge gaps and outlines further research directions necessary for the development of GPA as a potential therapeutic agent.</p>

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Unveiling the pharmacological landscape of geniposidic acid: mechanisms of action, therapeutic benefits, and scientific challenges

  • 期刊论文

  • 发表日期：

    2026年8月1日

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  • Lakshmi Narayana Ellutla,
  • Ashutosh Rajput,
  • Bidya Dhar Sahu

摘要

Geniposidic acid (GPA) is a bioactive iridoid glycoside mainly found in many traditional medicinal plants, including Eucommia ulmoides and Gardenia jasminoides. These plants are also commonly used in traditional diets and herbal teas throughout East Asia, particularly in China and Japan, where they are used to maintain well-being and protect the respiratory, cardiovascular, and renal systems. Despite the growing number of individual studies that highlight GPA’s therapeutic potential, to date, there has been a lack of a systematic, critical synthesis of current knowledge. The aim of this review is to summarize the available information regarding the natural sources, methods of extraction, chemical structure, and biological and therapeutic actions of GPA. Data were obtained from PubMed, Scopus, and Web of Science, as well as reports published up to 2025. Evidence shows that GPA exerts manifold biological activities. The pharmacological actions in various disease models, including inflammatory, metabolic syndromes, neurodegenerative, cardiovascular, renal, and hepatic diseases and their mechanisms of action were discussed. The protective actions of GPA are associated with modulation of multiple cellular signaling pathways, including NF-κB, NRF2/HO-1, PI3K/AKT, FXR, and TGF-β signaling, as well as inhibition of NLRP3 inflammasome activation. However, direct molecular target validation has only been demonstrated for selected pathways, particularly FXR and NLRP3, whereas most mechanistic evidence remains based on downstream signaling observations. Although preclinical studies in cells and animals demonstrate that GPA is effective, poor bioavailability remains one major limiting factor. Furthermore, comprehensive pharmacokinetic, toxicological, safety profiling, and well-designed clinical studies are required to support the clinical translation of GPA. This review identifies knowledge gaps and outlines further research directions necessary for the development of GPA as a potential therapeutic agent.